chr1-97805670-A-C

Variant names:

• chr1-97805670-A-C
• rs10493895
• NM_000110.4:c.233+22444T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000110.4(DPYD):​c.233+22444T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,578 control chromosomes in the GnomAD database, including 2,398 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2398 hom., cov: 31)
• Consequence: DPYD NM_000110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• Publications: 9 publications found

Genes affected

DPYD (HGNC:3012): (dihydropyrimidine dehydrogenase) The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Mutations in this gene result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

DPYD Gene-Disease associations (from GenCC):

• dihydropyrimidine dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYD	NM_000110.4	c.233+22444T>G		intron_variant	Intron 3 of 22	ENST00000370192.8	NP_000101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYD	ENST00000370192.8	c.233+22444T>G		intron_variant	Intron 3 of 22	1	NM_000110.4	ENSP00000359211.3
DPYD	ENST00000306031.5	c.233+22444T>G		intron_variant	Intron 3 of 5	1		ENSP00000307107.5

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24886 AN: 151462 Hom.: 2398 Cov.: 31

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.169

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.164 AC: 24879 AN: 151578 Hom.: 2398 Cov.: 31 AF XY: 0.164 AC XY: 12136 AN XY: 74076

African (AFR) AF: 0.0766 AC: 3171 AN: 41420

American (AMR) AF: 0.140 AC: 2117 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3468

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5170

South Asian (SAS) AF: 0.168 AC: 808 AN: 4812

European-Finnish (FIN) AF: 0.263 AC: 2777 AN: 10540

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14705 AN: 67700

Other (OTH) AF: 0.166 AC: 350 AN: 2104

Alfa AF: 0.194 Hom.: 3739

Bravo AF: 0.151

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.70
DANN	Benign	0.53
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10493895; hg19: chr1-98271226;